Elsevier

Neuroscience

Volume 132, Issue 1, 2005, Pages 193-201
Neuroscience

Mechanical and heat sensitization of cutaneous nociceptors in rats with experimental peripheral neuropathy

https://doi.org/10.1016/j.neuroscience.2004.12.036Get rights and content

Abstract

This study examined whether or not the properties of cutaneous nociceptive fibers are altered in the neuropathic state by comparing lumbars 5 and 6 spinal nerve ligation (SNL) rats with sham-operated controls. The rats with the unilateral SNL developed mechanical allodynia in the ipsilateral hind limb, whereas the sham group did not. Two to 5 weeks after the neuropathic or sham surgery, rats were subjected to single fiber-recording experiments to examine the properties of afferent fibers in the sural and plantar nerves. A total of 224 afferents in the C- and Aδ-ranges were characterized in the neuropathic and sham groups. Spontaneous activity was observed in 16 of 155 fibers in the neuropathic group and one of 69 fibers in the sham group. The response threshold of both the C- and Aδ-fibers to mechanical stimuli was lower in the neuropathic group than the sham group. The afferent fibers responsive to heat stimuli were all C-fibers, and none were Aδ-fibers. The response threshold of the C-fibers to the heat stimuli was lower in the neuropathic group than the sham group. The magnitude of the responses of both C- and Aδ-fibers to the suprathreshold intensity of the mechanical stimulus was greater in the neuropathic group than the sham group. However, the magnitude of the responses of C-fibers to the suprathreshold intensity of the heat stimulus in the neuropathic group was not different from that in the sham group. These results suggest that after a partial peripheral nerve injury, the nociceptors on the skin supplied by an uninjured nerve become sensitized to both mechanical and heat stimuli. This nociceptor sensitization can contribute to neuropathic pain.

Section snippets

Animals

A total of 78 young adult male rats (Sprague–Dawley; Harlan) weighing 150–350g were used in this study. The animals were housed in groups of three to four, with food and water available ad libitum, and were allowed to acclimate under a light/dark cycle for approximately 1 week prior to surgery and behavioral test. Behavioral testing was started with a habituation period, in which rats were placed in plexiglas cages for 30 min. The experiments were carried out in accordance with the National

Results

Before the left L5–L6 SNL, the rats exhibited no paw withdrawal responses to 10 applications of the VFF stimuli (24.5 mN bending-force) to the plantar surface of the hind paw. Two to 3 days after the left L5–L6 SNL, most of the rats (63 of 70) exhibited a paw withdrawal frequency of 40% or higher in response to the same VFF stimulus to the affected hind paw (61.2±9.8% on average). This increased mechanical sensitivity, which is believed to be a behavioral sign of mechanical allodynia, lasted

Discussion

In the present study, we examined the receptive properties of the C- and Aδ-afferents in the hind paw of a L5/L6 SNL neuropathy rat model, for which behavioral studies have previously shown an increase in the mechanical and heat sensitivity of the affected hind paw (Kim and Chung, 1992). In this model, our single fiber recording experiments demonstrated the sensitization of the cutaneous terminals of the C- and Aδ-afferents (presumably nociceptors) in the affected hind paw. This was evidenced

Conclusions

This study demonstrated that the nociceptors on the skin supplied by an uninjured nerve become sensitized after a partial peripheral nerve injury. Nociceptor sensitization was evidenced by 1) the increase in the incidence of spontaneous activity, 2) the reduction in the response thresholds to mechanical and heat stimuli, and 3) the increase in the magnitude of the responses to the supra-threshold mechanical stimulus. This nociceptor sensitization might account in part for the characteristic

Acknowledgments

This work was supported by a grant of the Stem Cell Research Center of 21 C Frontier Research Program, Ministry of Science and Technology (SC12060), Republic of Korea. This work is also supported in part by NIH grants NS 31680 and NS 11255.

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    1

    B. Shim and D.-W. Kim contributed equally to this work.

    2

    Present address: Department of Neurosurgery, John Hopkins University, 5-109 Meyer 600 N. Wolfe Street, Baltimore, MD 21287, USA.

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